Prostaglandins are mediators of pain, fever and other symptoms associated with inflammation. Prostaglandin E2 (PGE2) is the predominant eicosanoid detected in inflammation conditions. In addition, it is also involved in various physiological and/or pathological conditions such as hyperalgesia, uterine contraction, digestive peristalsis, awakeness, suppression of gastric acid secretion, blood pressure, platelet function, bone metabolism, angiogenesis or the like.
Four PGE2 receptor subtypes (EP1, EP2, EP3 and EP4) displaying different pharmacological properties have been cloned. The EP4 subtype, a Gs-coupled receptor, stimulates cAMP production, and is distributed in a wide variety of tissue suggesting a major role in PGE2-mediated biological events.
WO03/016254 and WO00/20371 describe carboxylic acids compounds as prostaglandin receptor antagonists.
Although substituted methyl benzamide compounds are described in WO03/030937, it relates to mitochondrial benzodiazepine receptor antagonists. Further, WO98/45268 and EP1229034 describe substituted nicotinamide compounds, however they relate to inhibitors of phosphodiesterases 4 isozymes. It would be desirable if there were provided a novel EP4 selective antagonist with potent binding activity by systemic administration, and both with potent EP4 receptor binding activity and with metabolic stability.